safety study of dna vaccine delivered by intradermal electroporation to treat colorectal cancer

Conditions: Colorectal Cancer

Summary: the purpose of this study is to evaluate the safety and immunogenicity of a cea dna immunisation approach in patients with colorectal cancer. the dna plasmid, tetwtcea, encodes wild type human cea fused to a tetanus toxoid t helper epitope. the vaccine will be delivered using an intradermal electroporation device, derma vax (cyto pulse sciences). the following will be assessed: * the efficiency of priming immunological responses to cea by intradermal administration of cea dna in combination with electroporation. * the efficiency of boosting immunological responses to cea by intradermal administration of cea dna in combination with electroporation in subjects already vaccinated with cea dna. * gm-csf will be administered to half of the subjects primed with cea dna in combination with electroporation and any possible adjuvant effects of gm-csf will be evaluated.


Eligibility criteria:
inclusion criteria: * histological confirmed ajcc stage ii or iii colorectal cancer * resection of the primary tumour without evidence of remaining macroscopic disease * allowable standard chemotherapy or radiotherapy in ajcc stage iii completed minimum 2 months prior study entry * patients recruited from vaccination with cea66 plasmid dna must have completed trial at 18 months if immune response is proven or proven to be non-immune responders in two consecutive immunoassays. * age \>18 years * karnofsky performance \>80% * life expectancy of greater than 6 months * normal organ and marrow function * normal thyroid function as measured by serum t3, t4 and tsh * normal echocardiogram regarding arrhythmias (chronic or treated atrial fibrillation allowed) * no concurrent treatment (chemotherapy or biological) may be planned during protocol treatment * women or men of reproductive potential must agree to use adequate contraception prior to study entry and for up to 3 months after the last injection * ability to understand and the willingness to sign an informed consent document exclusion criteria: * immunotherapy or systemic corticosteroids within 8 weeks prior to entering the study * chemotherapy or radiotherapy within 2 months prior to entering the study * known hypersensitivity to gm-csf * previous splenectomy or radiation therapy of the spleen * pregnancy or nursing * hiv seropositivity * uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic intracranial disease, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * history of severe neurological, cardiovascular, renal, hepatic, respiratory, bone marrow dysfunction, organ graft or autoimmune disease (treated or not) * concomitant medication with an anticoagulant (acetylsalicylic acid and low-molecular weight heparin in prophylactic dose allowed) * other malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage i or ii cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years * cardiac demand pacemakers or surgically implanted defibrillators. * patients that has any metal implants in the area of the injection, (e.g. shoulder implant in the upper arm or shoulder girdle)

Keywords: dna vaccine electroporation